Periodontal disease is an oral disease spreading across the world and one of major causes of tooth loss. Although some active ingredients can be mentioned against such a wound as to include periodontal disease, a demand still exists for compounds capable of accelerating wound healing.
Examples of the compounds that show the accelerating action of wound healing include agents, as an active ingredient, such as an extract from aloes or the like, an antibiotic, an anti-inflammatory agent, kallikrein, adenine, nicotinic acid, allantoin, vitamin A, zinc, a cAMP derivative (Patent Literature 1) and exogenous collagen (Patent Literature 2). In the conventional technique, the improvement of a formulation, etc., to improve the absorbability of such active ingredients had been actively practiced, however, recently, as various findings on the skin histology become clear, attempts to use epidermal growth factor (EGF) for postoperative wound healing have been made (Patent Literature 3).
When an agent is orally administered, a portion of the administered agent acts on the affected area, thereby making it difficult to obtain a sufficient effect and further leaving concern over the manifestation of side effects. Therefore, agents such as an external preparation, which act directly on the skin, are desired for therapy. Few wound healing accelerators, however, are available as an external preparation, and this makes skin wound healing difficult.
At present, as a wound healing accelerator which is commonly used for an external preparation, solcoseryl ointment containing as a main ingredient a calf blood extract, Actosin ointment containing as a main ingredient bucladesine sodium which is a cAMP derivative, and Fiblast spray containing as a main ingredient bFGF (basic fibroblast growth factor), are known. It is, however, required for therapy to apply such an accelerator to the affected area for a long time, and side effects, such as irritation/aching, redness, itching and the increase of exudation, have also been reported. Many of specific polyphenols as disclosed in the present specification, for example, proanthocyanidin and chlorogenic acid which are abundant in grapes and coffee, respectively, abound in familiarity with eating, and can constitute one characteristic feature of being highly safe even upon ingestion. In addition, it takes a certain extent of time for the above drugs to show the effect on fibroblasts, and the action of various growth factors (TGF-β, IL-1α and PDGF) including bFGF that the present inventors had previously tested became detectable on a fibroblast wound model (in vitro) after 24 hours of treatment (Non Patent Literature 1). Thus, any drug or the like to reveal its effect after several minutes of treatment has not been reported.
On the other hand, it has been known that a polyphenol acts as an antioxidant and has a suppressing effect on oxidative damage at inflamed sites in local tissues which are caused by reactive oxygen species produced by inflammatory cells such as neutrophils. A polyphenol is used for an external dermatologic agent, an agent for use in the oral cavity and the like (Patent Literatures 4-9 and Non Patent Literatures 2 and 3). However, it has not been confirmed that any specific polyphenol can accelerate wound healing.